随着九月的尾声悄然降临，本月关于胃癌研究的文献综述也如约而至。转眼间，我们迎来了祖国的生日——国庆节。在这个充满喜悦和期待的时刻，让我们共同祝愿伟大的祖国繁荣昌盛，国泰民安。同时，也愿大家在国庆假期中，无论是选择宅在家中享受宁静，还是选择外出旅行探索未知，都能拥有一段美好的记忆。
01
N Engl J Med (IF: 96.2; Q1). 2024 Sep 14.
doi: 10.1056/NEJMoa2405195. Online ahead of print.
Preoperative Chemoradiotherapy for Resectable Gastric Cancer
可切除胃癌的术前放化疗
Background: In Western countries, the current standard of care for resectable gastric cancer is perioperative chemotherapy. Preoperative chemoradiotherapy has been considered, but data are limited regarding this treatment as compared with perioperative chemotherapy alone.
Methods: We conducted an international, phase 3 trial in which patients with resectable adenocarcinoma of the stomach or gastroesophageal junction were randomly assigned to receive preoperative chemoradiotherapy plus perioperative chemotherapy or perioperative chemotherapy alone (control). In both groups, patients received either epirubicin, cisplatin, and fluorouracil or fluorouracil, leucovorin, oxaliplatin, and docetaxel both before and after surgery; the preoperative-chemoradiotherapy group also received chemoradiotherapy (45 Gy in 25 fractions of radiation, plus fluorouracil infusion). The primary end point was overall survival, and secondary end points included progression-free survival, pathological complete response, toxic effects, and quality of life.
Results: A total of 574 patients underwent randomization at 70 sites in Australasia, Canada, and Europe: 286 to the preoperative-chemoradiotherapy group and 288 to the perioperative-chemotherapy group. A higher percentage of patients in the preoperative-chemoradiotherapy group than in the perioperative-chemotherapy group had a pathological complete response (17% vs. 8%) and greater tumor downstaging after resection. At a median follow-up of 67 months, no significant between-group differences in overall survival or progression-free survival were noted. The median overall survival was 46 months with preoperative chemoradiotherapy and 49 months with perioperative chemotherapy (hazard ratio for death, 1.05; 95% confidence interval, 0.83 to 1.31), and the median progression-free survival was 31 months and 32 months, respectively. Treatment-related toxic effects were similar in the two groups.
Conclusions: The addition of preoperative chemoradiotherapy to perioperative chemotherapy did not improve overall survival as compared with perioperative chemotherapy alone among patients with resectable gastric and gastroesophageal junction adenocarcinoma. (Funded by the National Health and Medical Research Council and others; TOPGEAR ClinicalTrials.gov number, NCT01924819.).
2
JAMA (IF: 63.1; Q1). 2024 Sep 3;332(9):722-729.
doi: 10.1001/jama.2024.10852.
Germline CDH1 Variants and Lifetime Cancer Risk
胚系 CDH1 变异和终生癌症风险
Abstract
Importance: Approximately 1% to 3% of gastric cancers and 5% of lobular breast cancers are hereditary. Loss of function CDH1 gene variants are the most common gene variants associated with hereditary diffuse gastric cancer and lobular breast cancer. Previously, the lifetime risk of gastric cancer was estimated to be approximately 25% to 83% and for breast cancer it was estimated to be approximately 39% to 55% in individuals with loss of function CDH1 gene variants.
Objective: To describe gastric and breast cancer risk estimates for individuals with CDH1 variants.
Design, setting, and participants: Multicenter, retrospective cohort and modeling study of 213 families from North America with a CDH1 pathogenic or likely pathogenic (P/LP) variant in 1 or more family members conducted between January 2021 and August 2022.
Main outcomes and measures: Hazard ratios (HRs), defined as risk in variant carriers relative to noncarriers, were estimated for each cancer type and used to calculate cumulative risks and risks per decade of life up to age 80 years.
Results: A total of 7323 individuals from 213 families were studied, including 883 with a CDH1 P/LP variant (median proband age, 53 years [IQR, 42-62]; 4% Asian; 4% Hispanic; 85% non-Hispanic White; 50% female). In individuals with a CDH1 P/LP variant, the prevalence of gastric cancer was 13.9% (123/883) and the prevalence of breast cancer among female carriers was 26.3% (144/547). The estimated HR for advanced gastric cancer was 33.5 (95% CI, 9.8-112) at age 30 years and 3.5 (95% CI, 0.4-30.3) at age 70 years. The lifetime cumulative risk of advanced gastric cancer in male and female carriers was 10.3% (95% CI, 6%-23.6%) and 6.5% (95% CI, 3.8%-15.1%), respectively. Gastric cancer risk estimates based on family history indicated that a carrier with 3 affected first-degree relatives had a penetrance of approximately 38% (95% CI, 25%-64%). The HR for breast cancer among female carriers was 5.7 (95% CI, 2.5-13.2) at age 30 years and 3.9 (95% CI, 1.1-13.7) at age 70 years. The lifetime cumulative risk of breast cancer among female carriers was 36.8% (95% CI, 25.7%-62.9%).
Conclusions and relevance: Among families from North America with germline CDH1 P/LP variants, the cumulative risk of gastric cancer was 7% to 10%, which was lower than previously described, and the cumulative risk of breast cancer among female carriers was 37%, which was similar to prior estimates. These findings inform current management of individuals with germline CDH1 variants.
3
Lancet Oncol (IF: 41.6; Q1). 2024 Sep;25(9):e452-e463.
doi: 10.1016/S1470-2045(24)00180-3.
Improving individualised therapies in localised gastro-oesophageal adenocarcinoma
改善局限性胃食管腺癌的个体化治疗
Abstract
Despite our increased understanding of the biological and molecular aspects of gastro-oesophageal tumourigenesis, the identification of prognostic or predictive factors remains challenging. Patients with resectable gastric and oesophageal adenocarcinoma are often treated similarly after surgical resection, regardless of their tumour biology, clinical characteristics, and histological treatment response. Substantial progress has been made in the past 5 years in managing patients with gastric or oesophageal adenocarcinoma, including the use of immune checkpoint inhibitors and new targeted therapies, leading to substantial improvements in clinical outcomes. These advancements have primarily been established in advanced and metastatic disease, while the management framework for local and locoregional disease is just beginning to shift. We provide an overview of existing data on biomarkers and tumour-related and host-related factors that are relevant to stratify patients into low-risk and high-risk recurrence groups, both before and after surgery, paving the way for more personalised treatment approaches.
4
Gut (IF: 23.0; Q1). 2024 Sep 4:gutjnl-2024-332705.
doi: 10.1136/gutjnl-2024-332705. Online ahead of print.
Where are we with gastric cancer screening in Europe in 2024?
2024 年欧洲胃癌筛查进展如何？
Abstract
The absolute number of annual cases of gastric cancer in Europe is rising. The Council of the European Union has recommended implementation of gastric cancer screening for countries or regions with a high gastric cancer incidence and death rates. However, as of 2024 no organised gastric cancer screening programme has been launched in Europe.There are several ways to decrease gastric cancer burden, but the screen and treat strategy for Helicobacter pylori (H. pylori) seems to be the most appropriate for Europe. It has to be noted that increased use of antibiotics would be associated with this strategy.Only organised population-based cancer screening is recommended in the European Union, therefore gastric cancer screening also is expected to fulfil the criteria of an organised screening programme. In this respect, several aspects of screening organisation need to be considered before full implementation of gastric cancer prevention in Europe; the age range of the target group, test types, H. pylori eradication regimens and surveillance strategies are among them. Currently, ongoing projects (GISTAR, EUROHELICAN, TOGAS and EUCanScreen) are expected to provide the missing evidence. Feedback from the decision-makers and the potential target groups, including vulnerable populations, will be important to planning the programme.This paper provides an overview of the recent decisions of the European authorities, the progress towards gastric cancer implementation in Europe and expected challenges. Finally, a potential algorithm for gastric cancer screening in Europe is proposed.
5
Int J Surg (IF: 12.5; Q1). 2024 Sep 24.
doi: 10.1097/JS9.0000000000001768. Online ahead of print.
Development of a staging system for hepatoid adenocarcinoma of the stomach based on multicenter data: A retrospective cohort study: A Staging System for Hepatoid Adenocarcinoma of the Stomach
基于多中心数据的胃肝样腺癌分期系统的开发：回顾性队列研究：胃肝样腺癌分期系统
Abstract
Background: Hepatoid adenocarcinoma of the stomach (HAS) is a rare subtype of gastric cancer (GC) with a poor prognosis. Furthermore, the current pathological staging system for HAS does not distinguish it from that for common gastric cancer (CGC).
Methods: The clinicopathological data of 251 patients with primary HAS who underwent radical surgery at 14 centers in China from April 2004 to December 2019 and 5082 patients with primary CGC who underwent radical surgery at 2 centers during the same period were retrospectively analyzed. A modified staging system was established based on the differences in survival.
Results: After 1:4 propensity score matching (PSM), 228 patients with HAS and 828 patients with CGC were analyzed. Kaplan-Meier (K-M) analysis showed patients with HAS had a poorer prognosis compared with CGC. Multivariate analysis identified pN stage, CEA level, and perineural invasion (PNI) as independent prognostic factors in patients with HAS. A modified pT (mpT) staging was derived using recursive partitioning analysis (RPA) incorporating PNI and pT staging. The modified pathological staging system (mpTNM) integrated the mpT and the 8th American Joint Committee on Cancer (AJCC) pN definitions. Multivariate analysis showed that mpTNM stage outperformed other pathological variables as independent predictors of OS and RFS in patients with HAS. The mpTNM staging system exhibited significantly higher predictive accuracy for 3-year OS in patients with HAS (0.707, 95% CI: 0.650-0.763) compared to that of the 8th AJCC staging system (0.667, 95% CI: 0.610-0.723, P<0.05). Analysis using the Akaike information criterion favored the mpTNM staging system over the 8th AJCC staging system (824.69 vs. 835.94) regarding the goodness of fit. The mpTNM stages showed improved homogeneity in survival prediction (likelihood ratio: 41.51 vs. 27.10). Comparatively the mpTNM staging system outperformed the 8th AJCC staging system in survival prediction, supported by improvements in the net reclassification index (NRI: 47.7%) and integrated discrimination improvement (IDI: 0.083, P<0.05). Time-dependent ROC curve showed that the mpTNM staging system consistently outperformed the 8th AJCC staging system with increasing observation time.
Conclusion: The mpTNM staging system exhibited superior postoperative prognostic accuracy for patients with HAS compared to the 8th AJCC staging system.
6
Int J Surg (IF: 12.5; Q1). 2024 Sep 24.
doi: 10.1097/JS9.0000000000002090. Online ahead of print.
Extensive intraoperative peritoneal lavage with surgery, compared to surgery alone, for patients diagnosed with gastric cancer: A systematic review and meta-analysis of randomized controlled trials
对于诊断为胃癌的患者，与单独手术相比，手术期间进行广泛的术中腹腔灌洗：随机对照试验的系统评价和荟萃分析
Abstract
Background: Gastric cancer ranks as the fifth most frequently diagnosed cancer and the seventh most prevalent overall. The lifetime risk of developing gastric cancer is 1.87% for males and 0.79% for females worldwide.
Aim: This systematic review and meta-analysis aimed to determine whether Extensive Intraoperative Peritoneal Lavage (EIPL) provides short-term benefits or improved survival outcomes for patients undergoing gastrectomy.
Methods: A comprehensive search spanned PubMed, Embase, Cochrane Library, clinicaltrials.gov, and Web of Science, from their inception up to October 2023, adhering to predefined inclusion and exclusion criteria. The quality of the studies was analyzed using the Cochrane Collaboration Risk of Bias Tool. Data analysis was done using Review Manager 5.3, utilizing a random-effects model.
Results: Our analysis incorporated seven randomized controlled trials with 2602 patients. The follow-up time for all outcomes varied from 30-60 months. For our primary outcomes, EIPL demonstrated a significant benefit over surgery alone in terms of recurrence (RR=0.73; 95% CI: 0.65 to 0.83, P<0.00001) and postoperative complications (RR=0.67; 95% CI: 0.51 to 0.87, P=0.003). For our secondary outcomes, postoperative hospital stay (MD=-0.35; 95% CI: -1.11 to 0.41; P-value=0.37), 3-year overall survival (OR=1.44; 95% CI 0.84 to 2.47; P-value=0.19), 3-year disease-free survival (HR=0.93; 95% CI: 0.78 to 1.13; P-value=0.48), and time to first flatus (MD=-0.17; 95% CI: -0.35 to 0.01; P-value=0.06), no statistically significant differences were observed between the EIPL and control groups.
Conclusion: While there is a marginal difference in survival outcomes, EIPL holds promise in significantly reducing overall cancer recurrence and suggests an enhancement in postoperative recovery.
7
Int J Surg (IF: 12.5; Q1). 2024 Sep 1;110(9):5574-5584.
doi: 10.1097/JS9.0000000000001626.
Finding the minimum number of retrieved lymph nodes and negative lymph nodes in gastric cancer surgery: a real-world study
寻找胃癌手术中取出的淋巴结和阴性淋巴结的最少数量：一项真实世界研究
Abstract
Background: Lymph node retrieval deficiency can lead to understagement and postoperative cancer recurrence, it is crucial to establish the standard number of retrieved lymph nodes (rLNs) and negative lymph nodes (nLNs) for patients undergoing gastrectomy.
Methods: Patients who has gastric adenocarcinoma and underwent either radical subtotal gastrectomy (RSG) or radical total gastrectomy (RTG) between 2000 and 2022 were retrospectively included. The authors utilized restricted cubic spline (RCS) analysis to determine the ideal threshold for rLNs and nLNs. Survival analysis was conducted using Kaplan-Meier (KM) curves, log-rank tests and forest plots. Propensity score matching (PSM) was utilized to balance parameters between two groups. The median follow-up time for this study was 3095 days.
Results: Our study found that there are significant tumor characteristic differences between RSG and RTG. For patients with N0-N3a stage undergoing RSG, retrieving greater than or equal to 24 lymph nodes intraoperatively were associated with better prognosis both before and after PSM [overall survival (OS): P <0.001, P =0.019]; whereas for N3b stage, at least 32 rLNs were required (OS: P =0.006, P =0.023). Similarly, for patients with N0-N3a stage undergoing RTG, retrieving greater than or equal to 27 lymph nodes intraoperatively were associated with better prognosis both before and after PSM (OS: P <0.001, P =0.047); whereas for N3b stage, at least 34 rLNs were required (OS: P <0.001, P =0.003). Additionally, for patients undergoing RSG, having greater than or equal to 21 nLNs (OS: P <0.001, P =0.013), and for those undergoing RTG, having greater than or equal to 22 nLNs (OS: P <0.001, P <0.001), were also associated with better prognosis both before and after PSM.
Conclusions: For patients receiving RSG, rLNs should reach 24 when lymph nodes are limited, and 32 when lymph node metastasis is more extensive, with a minimum number of nLNs ideally reaching 21. Similarly, for patients receiving RTG, rLNs should reach 27 when lymph nodes are limited, 34 when lymph node metastasis is more extensive, and a minimum number of nLNs ideally reaching 22.
8
Clin Cancer Res (IF: 10.0; Q1). 2024 Sep 26.
doi: 10.1158/1078-0432.CCR-23-3523. Online ahead of print.
The Tumour Immune Microenvironment Drives Survival Outcomes and Therapeutic Response in an Integrated Molecular Analysis of Gastric Adenocarcinoma
胃腺癌的综合分子分析中肿瘤免疫微环境驱动生存结果和治疗反应
Abstract
Purpose: We performed an integrated analysis of molecular classification systems proposed by The Cancer Genome Atlas (TCGA), the Asian Cancer Research Group (ACRG) and the Tumour Microenvironment Score (TME) to identify which classification scheme(s) are most promising to pursue in subsequent translational investigations.
Experimental design: Supervised machine learning classifiers were created using 10-fold nested cross-validation for TCGA, ACRG and TME subtypes and applied to 2,202 gastric cancer patients from 11 separate publicly available datasets. Overall survival was assessed with a multivariable Cox proportional hazards model. A propensity score matched analysis was performed to evaluate the subgroup effect of adjuvant chemotherapy on molecular subtypes. A public external cohort comprised of metastatic gastric cancer treated with immunotherapy was used to externally validate the molecular subtypes.
Results: Classification models for TCGA, ACRG and TME achieved an accuracy ± standard deviation of 89.5% ± 0.04, 84.7% ± 0.04 and 89.3% ± 0.02, respectively. We identified the TME score as the only significantly prognostic classification system (HR 0.54 [95% CI 0.39, 0.74], global Wald test p<0.001). In our subgroup analysis, patients who received adjuvant chemotherapy achieved greater survival with increasing TME score (HR 0.47 [95% CI 0.29, 0.74], interaction p<0.05). The combination of TME High and microsatellite instability (MSI) scores significantly outperformed MSI as a univariable predictor of immunotherapy response.
Conclusions: We conclude that the Tumour Microenvironment Score is a predominate driver of prognosis as well as chemotherapy and immunotherapy-related outcomes in gastric cancer. This paper provides a foundation for additional analyses and translational work.
9
Clin Cancer Res (IF: 10.0; Q1). 2024 Sep 25.
doi: 10.1158/1078-0432.CCR-24-1853. Online ahead of print.
Preclinical Evaluation of AZD6422, an Armored Chimeric Antigen Receptor T Cell Targeting CLDN18.2 in Gastric, Pancreatic, and Esophageal Cancer
AZD6422（一种靶向 CLDN18.2 的嵌合抗原受体 T 细胞）在胃癌、胰腺癌和食管癌中的临床前评估
Abstract
Purpose: CLDN18.2 is a surface membrane protein crucial for maintaining tight junctions in gastric mucosal cells and is highly expressed in gastric, esophageal, and pancreatic cancers. Thus, CLDN18.2 is suited for exploration as a clinical target for chimeric antigen receptor T-cell (CAR-T) therapy in these indications. Although CAR-T therapies show promise, a challenge faced in their development for solid tumors is the immunosuppressive tumor microenvironment, often characterized by the presence of immune and stromal cells secreting high levels of transforming growth factor beta (TGF-β). Addition of TGF-β armoring can potentially expand CAR-T activity in solid tumors. We report on the preclinical development of a CLDN18.2-targeting CAR-T showing effectiveness in CLDN18.2-positive gastric, esophageal, and pancreatic tumor models.
Experimental design: The lead lentivirus product contains a unique single-chain variable fragment, CD28 and CD3z costimulatory and signaling domains, and dominant negative TGF-β receptor armoring, enhancing targeting and safety and counteracting suppression. We developed a shortened cell manufacturing process to enhance the potency of the final product, AZD6422.
Results: AZD6422 exhibited significant antitumor activity and tolerability in multiple patient-derived tumor xenograft models with various CLDN18.2 and TGF-β levels, as determined by immunohistochemistry. Efficacy of armored CAR-Ts in tumor models with elevated TGF-β was increased in vitro and in vivo. In vitro restimulation assays established greater persistence and cytolytic function of AZD6422 compared with a traditionally manufactured CAR-T.
Conclusions: AZD6422 was safe and efficacious in patient-derived, CLDN18.2-positive murine models of gastrointestinal cancers. Our data support further clinical development of AZD6422 for patients with these cancers.
10
Clin Cancer Res (IF: 10.0; Q1). 2024 Sep 13;30(18):4044-4054.
doi: 10.1158/1078-0432.CCR-24-0742.
Phase II Trial of HER-Vaxx, a B-cell Peptide-Based Vaccine, in HER2-Overexpressing Advanced Gastric Cancer Patients Under Platinum-Based Chemotherapy (HERIZON)
HER-Vaxx（一种 B 细胞肽疫苗）在接受铂类化疗的 HER2 过表达晚期胃癌患者中进行的 II 期试验 (HERIZON)
Purpose: A multicenter, randomized, open-label, phase II study (HERIZON; NCT02795988) was conducted to evaluate the clinical and immunologic efficacy of HER-Vaxx (IMU-131), a B-cell, peptide-based vaccine targeting HER2 overexpressed in 6% to 30% of gastroesophageal adenocarcinomas (GEA).
Patients and methods: Patients (n = 36) with GEA were treated with standard-of-care chemotherapy (n = 17) or HER-Vaxx plus chemotherapy (n = 19), using the recommended phase 2 dose for the vaccine. Overall survival (OS; primary endpoint), safety, progression-free survival (PFS), clinical response (secondary endpoints), and vaccine-induced HER2-specific antibody levels in serum and correlation with tumor response rates (exploratory endpoints) were investigated.
Results: A 40% OS benefit [HR, 0.60; median OS, 13.9 months; 80% confidence interval (CI), 7.52-14.32] for patients treated with HER-Vaxx plus chemotherapy compared with OS of 8.31 months (80% CI, 6.01-9.59) in patients that received chemotherapy alone. A 20% PFS difference was obtained for the vaccination arm (HR, 0.80; 80% CI, 0.47, 1.38). No additional toxicity due to HER-Vaxx was observed. The vaccine-induced high levels of HER2-specific total IgG and IgG1 antibodies (P < 0.001 vs. controls) that significantly correlated with tumor reduction (IgG, P = 0.001; IgG1, P = 0.016), had a significant capacity in inhibiting phosphorylation of the intracellular HER2-signaling pathways, mediated antibody-dependent cellular cytotoxicity, and decreased immunosuppressive FOXP3+ regulatory T cells.
Conclusions: HER-Vaxx plus standard chemotherapy exhibits an excellent safety profile and improves OS. Furthermore, vaccine-induced immune response was significantly associated with reduced tumor size compared with standard-of-care chemotherapy. The presented vaccination approach may substitute for treatment with trastuzumab, upon unavailability or toxicity, based on further evidence of equivalent treatment efficacy.
11
J Natl Cancer Inst (IF: 9.9; Q1). 2024 Sep 14:djae227.
doi: 10.1093/jnci/djae227. Online ahead of print.
Histopathological response to chemotherapy and survival of mucinous type gastric cancer
粘液型胃癌化疗的组织病理学反应和生存
Background: Data on the clinicopathological characteristics of mucinous gastric cancer (muc-GC) are limited. This study compares the clinical outcome and response to chemotherapy between patients with resectable muc-GC, intestinal (int-GC) and diffuse (dif-GC) gastric cancer.
Methods: Patients from the D1/D2 study or the CRITICS trial were included in exploratory surgery-alone (SAtest) or chemotherapy test (CTtest) cohorts. Real-world data from the Netherlands Cancer Registry on patients treated between with surgery-alone (SAvalidation), and receiving preoperative chemotherapy with or without postoperative treatment (CTvalidation) were used for validation. Histopathological subtypes were extracted from pathology reports filed in the Dutch Pathology Registry and correlated with tumor regression grade (TRG) and relative survival (RS).
Results: In SAtest (n = 549) and SAvalidation (n = 8062) cohorts, muc-GC patients had a five-year RS of 39% and 31%, similar to or slightly better than dif-GC (43% and 29%, p = .52 and p = .011), but worse than int-GC (55% and 42%, p = .11 and p < .001). In CTtest (n = 651) and CTvalidation (n = 2889) cohorts, muc-GC showed favorable TRG (38% and 44% (near-)complete response) compared to int-GC (26% and 35%) and dif-GC (10% and 28%, p < .001 and p = .005). The 5-year RS in CTtest and CTvalidation cohorts for muc-GC (53% and 48%) and int-GC (58% and 59%) was significantly better compared to dif-GC (35% and 38%, p = .004 and p < .001).
Conclusion: Recognizing and incorporating muc-GC into treatment decision-making of resectable GC can lead to more personalized and effective approaches, given its favorable response to preoperative chemotherapy in relation to int-GC and dif-GC and its favorable prognostic outcomes in relation to dif-GC.
12
Pharmacol Res (IF: 9.1; Q1). 2024 Sep 7:208:107401.
doi: 10.1016/j.phrs.2024.107401. Online ahead of print.
Glucagon-like peptide-1 receptor agonists and risk of gastrointestinal cancers: A systematic review and meta-analysis of randomized controlled trials
胰高血糖素样肽 1 受体激动剂与胃肠道肿瘤的风险：随机对照试验的系统评价和荟萃分析
Background: Glucagon-like peptide-1 receptor agonists (GLP-1 RAs) are commonly used for glucose lowering and weight-loss. However, their association with gastrointestinal cancer remains uncertain. This meta-analysis assesses the risk of gastrointestinal cancer in patients treated with GLP-1 RAs.
Methods: We searched Medline/PubMed, Embase, and Scopus databases from inception to November 15, 2023, for randomized controlled trials (RCTs) with at least 24 weeks of safety follow-up. Pooled risk ratios (RRs) were calculated using fixed- and random-effect models. Risk of bias was assessed using the revised Cochrane risk-of-bias tool, and certainty of evidence was determined using the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) framework.
Results: We included 90 RCTs with 124,791 participants, with an average follow-up of 3.1 years per participant. No significant association was found between GLP-1 RAs and the risk of any gastrointestinal cancer (RRrandom=0.99, 95 % CI: 0.86-1.13), or site-specific gastrointestinal cancers including biliary tract (RR=0.98, 0.54-1.78), colorectal (RR=1.13, 0.92-1.39), gallbladder (RR=1.32, 0.43-4.00), gastric (RR=0.88, 0.58-1.33), hepatic (RR=0.79, 0.51-1.21), oesophageal (RR=0.70, 0.38-1.28), pancreatic (RR=1.05, 0.77-1.43), and small intestine cancer (RR=0.78, 0.20-3.04). The corresponding absolute risk differences excluded important impacts on risk. Additional analyses, limited to placebo-controlled trials, high-dose studies, or those with a follow-up duration of ≥5 years, confirmed these findings. Risk of bias was generally low and the certainty of evidence was high for all outcomes.
Conclusions: This meta-analysis found no significant impact of GLP-1 RAs on gastrointestinal cancer risk. Long-term safety monitoring of these agents remains important.
Systematic review registration: CRD42023476762.
13
Chin Med J (Engl) (IF: 7.5; Q1). 2024 Sep 25.
doi: 10.1097/CM9.0000000000003303. Online ahead of print.
Neoadjuvant sintilimab and apatinib combined with perioperative FLOT chemotherapy for locally advanced gastric cancer: a prospective, single-arm, phase II study
新辅助信迪利单抗和阿帕替尼联合围术期FLOT化疗治疗局部进展期胃癌：一项前瞻性、单臂、II期研究
No abstract available
14
Ann Surg (IF: 7.5; Q1). 2024 Sep 2.
doi: 10.1097/SLA.0000000000006503. Online ahead of print.
Laparoscopic Pylorus Preserving Gastrectomy vs Distal Gastrectomy for Early Gastric Cancer; A Multicenter Randomized Controlled Trial (KLASS-04)
腹腔镜保留幽门胃切除术与远端胃切除术治疗早期胃癌；多中心随机对照试验 (KLASS-04)
Objective: To evaluate the long-term outcomes of laparoscopic pylorus preserving gastrectomy (LPPG) with laparoscopic distal gastrectomy (LDG) for early gastric cancer (EGC).
Summary background data: PPG is considered as a function preserving surgery for EGC. However, there has been no multicenter randomized controlled trial comparing PPG with DG until now.
Methods: A multicenter randomized controlled trial (KLASS-04) with 256 patients with cT1N0M0 gastric cancer located in the mid portion of the stomach was conducted. The primary endpoint was the incidence of dumping syndrome at postoperative 1 year. Secondary endpoints included survival and recurrence, gallstone formation, nutritional parameters, gastroscopic findings, and quality of life (QOL) for 3 years.
Results: In the intention-to-treat analyses, there was no difference in the incidence of dumping syndrome at one year postoperatively (13.2% in LPPG vs. 15.8% in LDG, P=0.622). Gallstone formation after surgery was significantly lower in LPPG than in LDG (2.33% vs. 8.66%, P=0.026). Hemoglobin (+0.01 vs. -0.76 gm/dL, P<0.001) and serum protein (-0.15 vs. -0.35 gm/dL, P=0.002) were significantly preserved after LPPG. However, reflux esophagitis (17.8% vs. 6.3%, P=0.005) and grade IV delayed gastric emptying (16.3% vs. 3.9%, P=0.001) were more common in LPPG. Changes in body weight and postoperative QOL were not significantly different between groups. Three-year overall survival and disease-free survival were not different (1 case of recurrence of in each group, P=0.98).
Conclusions: LPPG can be used as an alternative surgical option for cT1N0M0 gastric cancer in the mid portion of the stomach.
15
ESMO Open (IF: 7.1; Q1). 2024 Sep 16;9(9):103681.
doi: 10.1016/j.esmoop.2024.103681. Online ahead of print.
Phase I PIANO trial-PIPAC-oxaliplatin and systemic nivolumab combination for gastric cancer peritoneal metastases: clinical and translational outcomes
I 期 PIANO 试验 - PIPAC-奥沙利铂和纳武利尤单抗联合系统治疗胃癌腹膜转移：临床和转化结果
Introduction: Pressurized intraperitoneal aerosol chemotherapy-oxaliplatin (PIPAC-OX) induces direct DNA damage and immunogenic cell death in patients with gastric cancer peritoneal metastases (GCPM). Combining PIPAC-OX with immune checkpoint inhibition remains untested. We conducted a phase I first-in-human trial evaluating the safety and efficacy of PIPAC-OX combined with systemic nivolumab (NCT03172416).
Methods: Patients with GCPM who experienced disease progression on at least first-line systemic therapy were recruited across three centers in Singapore and Belgium. Patients received PIPAC-OX at 90 mg/m2 every 6 weeks and i.v. nivolumab 240 mg every 2 weeks. Translational studies were carried out on GCPM samples acquired during PIPAC-OX procedures.
Results: In total, 18 patients with GCPM were prospectively recruited. The PIPAC-OX and nivolumab combination was well tolerated with manageable treatment-related adverse events, although one patient suffered from grade 4 vomiting. At second and third PIPAC-OX, respectively, the median decrease in peritoneal cancer index (PCI) was -5 (interquartile range: -12 to +1) and -7 (interquartile range: -6 to -20) and peritoneal regression grade 1 or 2 was observed in 66.7% (6/9) and 100% (3/3). Translational analyses of 43 GCPM samples revealed enrichment of immune/stromal infiltration and inflammatory signatures in peritoneal tumors after PIPAC-OX and nivolumab. M2 macrophages were reduced in treated peritoneal tumor samples while memory CD4+, CD8+ central memory and naive CD8+ T-cells were increased.
Conclusions: The first-in-human trial combining PIPAC-OX and nivolumab demonstrated safety and tolerability, coupled with enhanced T-cell infiltration within peritoneal tumors. This trial sets the stage for future combinations of systemic immunotherapy with locoregional intraperitoneal treatments.
16
BMC Med (IF: 7.0; Q1). 2024 Sep 4;22(1):364.
doi: 10.1186/s12916-024-03594-7.
The spatiotemporal associations between esophageal and gastric cancers provide evidence for its joint endoscopic screening in China: a population-based study
食管癌和胃癌之间的时空关联性为中国联合内镜筛查提供证据：一项基于人群的研究
Background: The spatiotemporal epidemiological evidence supporting joint endoscopic screening for esophageal cancer (EC) and gastric cancer (GC) remains limited. This study aims to identify combined high-risk regions for EC and GC and determine optimal areas for joint and separate endoscopic screening.
Methods: We analyzed the association of incidence trends between EC and GC in cancer registry areas across China from 2006 to 2016 using spatiotemporal statistical methods. Based on these analyses, we divided different combined risk regions for EC and GC to implement joint endoscopic screening.
Results: From 2006 to 2016, national incidence trends for both EC and GC showed a decline, with an average annual percentage change of -3.15 (95% confidence interval [CI]: -5.33 to -0.92) for EC and -3.78 (95% CI: -4.98 to -2.56) for GC. A grey comprehensive correlation analysis revealed a strong temporal association between the incidence trends of EC and GC, with correlations of 79.00% (95% CI: 77.85 to 80.14) in males and 77.62% (95% CI: 76.50 to 78.73) in females. Geographic patterns of EC and GC varied, demonstrating both homogeneity and heterogeneity across different regions. The cancer registry areas were classified into seven distinct combined risk regions, with 33 areas identified as high-risk for both EC and GC, highlighting these regions as priorities for joint endoscopic screening.
Conclusion: This study demonstrates a significant spatiotemporal association between EC and GC. The identified combined risk regions provide a valuable basis for optimizing joint endoscopic screening strategies for these cancers.
17
Int J Radiat Oncol Biol Phys (IF: 6.4; Q1). 2024 Sep 3:S0360-3016(24)03319-4.
doi: 10.1016/j.ijrobp.2024.08.042. Online ahead of print.
Phase I Trial of Total Neoadjuvant Therapy with Short Course Chemoradiotherapy followed by Chemotherapy for Patients with Potentially Resectable Gastric Cancer
对潜在可切除胃癌患者进行短程放化疗后序贯化疗的全程新辅助治疗的 I 期试验
Background: The purpose of this phase I trial was to evaluate the safety and toxicity of preoperative short-course chemoradiotherapy (CRT) as part of total neoadjuvant therapy (TNT) for patients with potentially resectable gastric or gastroesophageal adenocarcinoma.
Methods: Patients were enrolled between March 2021 and December 2022 and received CRT (30 Gy radiation in 10 fractions with concurrent capecitabine or 5-fluorouracil), then received systemic therapy for 2 months, and then underwent surgery. The primary endpoint was CRT safety; secondary endpoints were pathologic complete response (pCR), perioperative complications, and overall survival (OS).
Results: Of the 24 patients enrolled in the trial, 10 (42%) had bleeding, 3 (13%) had gastric outlet obstruction, and 2 (8%) had cirrhosis. Twelve patients (50%) had clinical nodal involvement. Twenty patients (83%) had poorly differentiated tumors, and 13 (54%) had signet ring cell histology. All patients completed CRT. CRT treatment-related toxic effects included grade 3 lymphopenia in 7 patients (29%), grade 4 lymphopenia in 1 (4%), and grade 3 anemia in 1 (4%). After CRT, 22 patients (92%) received chemotherapy, 1 patient (4%) with a microsatellite instability-high tumor received immunotherapy, and 1 patient (4%) underwent resection without systemic therapy. All patients underwent attempted resection, and gastrectomy was performed in 20 (83%). The R0 resection rate was 95%. %. Two patients had pCR, and an additional 5 had ≤1% viable tumor. Three patients had surgical complications (grade I in 1 patient [4%], grade IIIb in 1 [4%], and grade IVa in 1 [4%]); no patients died within 90 days. The median follow-up time was 28 months, and median OS was not reached. The 1- and 3-year OS rates were 96% and 85%, respectively.
Conclusion: Short-course CRT may be safely used as part of planned TNT for patients with potentially resectable gastric or gastroesophageal adenocarcinoma. The promising rates of treatment completion, pathologic response, and OS support further research of TNT for gastric cancer.
18
Transl Res (IF: 6.4; Q1). 2024 Sep 9:S1931-5244(24)00167-1.
doi: 10.1016/j.trsl.2024.09.001. Online ahead of print.
Diagnostic, Prognostic, and Predictive Biomarkers in Gastric Cancer: from Conventional to Novel Biomarkers
胃癌的诊断、预后和预测生物标志物：从传统生物标志物到新型生物标志物
Gastric cancer is a major health concern worldwide. The survival rate of Gastric cancer greatly depends on the stage at which it is diagnosed. Early diagnosis is critical for improving survival outcomes. To improve the chances of early diagnosis, regular screening tests, such as an upper endoscopy or barium swallow, are recommended for individuals at a higher risk due to factors like family history or a previous diagnosis of gastric conditions. Biomarkers can be detected and measured using non-invasive methods such as blood tests, urine tests, breath analysis, or imaging techniques. These non-invasive approaches offer many advantages, including convenience, safety, and cost-effectiveness, making them valuable tools for disease diagnosis, monitoring, and research. Biomarker-based tests have emerged as a useful tool for identifying gastric cancer early, monitoring treatment response, assessing the recurrence risk, and personalizing treatment plans. In this current review, we have explored both classical and novel biomarkers for gastric cancer. We have centralized their potential clinical application and discussed the challenges in Gastric cancer research.
19
Cancer (IF: 6.1; Q1). 2024 Sep 17.
doi: 10.1002/cncr.35566. Online ahead of print.
Phase 1 trial of intraperitoneal paclitaxel in patients with gastric adenocarcinoma and carcinomatosis or positive cytology
腹腔注射紫杉醇治疗胃腺癌和癌变或细胞学阳性患者的 1 期试验
Abstract
Background: The purpose of this phase 1 trial was to evaluate the safety and toxicity of repeated normothermic intraperitoneal paclitaxel (PTX) for patients with gastric cancer metastatic to the peritoneum.
Methods: A Bayesian optimal interval design was used to prospectively identify the safety and tolerability of escalating doses of intraperitoneal paclitaxel at weekly treatments for 3 weeks, followed by a 1-week break, and then three additional treatments. The primary objective was to define the maximum tolerated dose. Secondary end points included safety, tolerability, and antitumor activity.
Results: A total of 25 patients were treated between January 2020 and April 2023. Five dose-limiting toxicities were observed at 100 mg/m2. Treatment-related grade 3-4 toxicity included leukopenia (32%) and neutropenia (32%). Seven patients required a schedule change to every other week treatments. The maximum tolerated dose for intraperitoneal PTX was 100 mg/m2. The peritoneum post-intraperitoneal PTX demonstrated progression in five (20%), stable disease in five (20%), improvement in 10 (40%), and not evaluable in five (20%). Eight patients (32%) had resolution of their peritoneal disease and seven (28%) underwent attempted resection. The median overall survival (OS) from the diagnosis of metastatic disease was 18.8 months and from the date of treatment initiation was 10.8 months. One-, 2-, and 3-year OS rates from the diagnosis of metastatic disease were 84%, 38%, and 25%, respectively.
Conclusions: Paclitaxel may be safely used at intraperitoneal doses of 100 mg/m2. Neutropenia associated with weekly treatments was common. Peritoneal complete clinical response rates with multimodality therapy including PTX were promising.
20
Cell Death Discov (IF: 6.1; Q1). 2024 Sep 3;10(1):393.
doi: 10.1038/s41420-024-02167-0.
Enhancing antitumor efficacy of CLDN18.2-directed antibody-drug conjugates through autophagy inhibition in gastric cancer
通过抑制胃癌自噬增强 CLDN18.2 导向的抗体偶联药物的抗肿瘤功作用
Abstract
Claudin18.2 (CLDN18.2) is overexpressed in cancers of the digestive system, rendering it an ideal drug target for antibody-drug conjugates (ADCs). Despite many CLDN18.2-directed ADCs undergoing clinical trials, the inconclusive underlying mechanisms pose a hurdle to extending the utility of these agents. In our study, αCLDN18.2-MMAE, an ADC composed of an anti-CLDN18.2 monoclonal antibody and the tubulin inhibitor MMAE, induced a dose-dependent apoptosis via the cleavage of caspase-9/PARP proteins in CLDN18.2-positive gastric cancer cells. It was worth noting that autophagy was remarkably activated during the αCLDN18.2-MMAE treatment, which was characterized by the accumulation of autophagosomes, the conversion of autophagy marker LC3 from its form I to II, and the complete autophagic flux. Inhibiting autophagy by autophagy inhibitor LY294002 remarkably enhanced αCLDN18.2-MMAE-induced cytotoxicity and caspase-mediated apoptosis, indicating the cytoprotective role of autophagy in CLDN18.2-directed ADC-treated gastric cancer cells. Combination with an autophagy inhibitor significantly potentiated the in vivo antitumoral efficacy of αCLDN18.2-MMAE. Besides, the Akt/mTOR pathway inactivation was demonstrated to be implicated in the autophagy initiation in αCLDN18.2-MMAE-treated gastric cancer cells. In conclusion, our study highlighted a groundbreaking investigation into the mechanism of the CLDN18.2-directed ADC, focusing on the crucial role of autophagy, providing a novel insight to treat gastric cancer by the combination of CLDN18.2-directed ADC and autophagy inhibitor.
21
Gastric Cancer (IF: 6.0; Q1). 2024 Sep 4.
doi: 10.1007/s10120-024-01545-y. Online ahead of print.
Survival among patients cured from gastric adenocarcinoma compared to the background population
胃腺癌治愈患者与背景人群的生存率比较
Abstract
Background: It is unknown if gastric adenocarcinoma survivors have longer, shorter, or similar survival compared to the background population. This knowledge could contribute to evidence-based monitoring strategies, healthcare recommendations, and information for patients and families.
Methods: This population-based cohort study included all patients who underwent gastrectomy for gastric adenocarcinoma between 2006-2015 in Sweden and survived ≥ 5 years after surgery. They were followed up until death, postoperative year 10, or end of study period (31 December, 2020). Division of the observed by the expected survival yielded relative survival rates with 95% confidence intervals (CIs) using the life table method. The expected survival was derived from the entire Swedish population of the corresponding age, sex, and calendar year. Data came from medical records and nationwide registers.
Results: The survival among all 767 gastric adenocarcinoma survivors was shorter than the expected. The reduction in relative survival increased for each follow-up year, from 97.3% (95% CI 95.4-99.1%) year 6 to 86.6% (95% CI 82.3-90.9%) year 10. The decline in relative survival was more pronounced among patients who had gastrectomy in earlier calendar years (82.9% [95% CI 77.4-88.4%] year 10 for years 2011-2015), shorter education (85.2% [95% CI 77.4-93.0%] year 10 for education ≤ 9 years), more comorbidities (78.0% [95% CI 63.9-92.0%] year 10 for Charlson comorbidity score ≥ 2), and no neoadjuvant therapy (83.2% [95% CI 77.4-89.0%] year 10).
Conclusion: Gastric adenocarcinoma survivors seem to have poorer survival than the corresponding background population, particularly in certain subgroups.
22
Gastric Cancer (IF: 6.0; Q1). 2024 Sep 28.
doi: 10.1007/s10120-024-01553-y. Online ahead of print.
Clinical epidemiology of the endoscopic, laparoscopic, and surgical resection of malignant gastric tumors in Japan, 2014-2021: a retrospective study using open data from a national claims database
2014-2021 年日本胃恶性肿瘤内窥镜、腹腔镜和手术切除的临床流行病学：使用国家理赔数据库开放数据的回顾性研究
Abstract
Background: Gastric cancer is a common malignancy with a high incidence in East Asia. Gastric resection ranges from endoscopic resection to open total gastrectomy. However, nationwide data are lacking.
Methods: This observational study analyzed data from the publicly accessible National Database of Health Insurance Claims and Specific Health Checkups, which includes most national health insurance claims data in Japan. Trends in the types of resection performed for malignant gastric tumors between 2014 and 2021, patients' age and sex distributions, and regional disparities were investigated.
Results: The annual number of resections was highest in 2015 (109,000) and lowest in 2020 (90,000) after the COVID-19 pandemic. The proportion of endoscopic resections increased from 47% in 2014 to 57% in 2021 while that of total gastrectomies decreased from 17 to 10%. In 2021, 70% of patients who underwent resection were men. That year, 83.8% of all patients who underwent any type of gastric resection and 87.1% of those who underwent endoscopic submucosal dissection were aged ≥ 65 years. The annual incidence of gastric resection per million population was highest in Tottori (n = 1236) and lowest in Okinawa (n = 251). The proportion of endoscopic resections was highest in Miyagi (66%) and lowest in Aichi (45%) and that of open surgery was highest in Aomori (36%) and lowest in Wakayama (5%).
Conclusions: Gastric malignancy is increasingly treated by endoscopic submucosal dissection rather than open total gastrectomy. However, regional disparities remain in resection type. Standardization of treatment and a more even distribution of specialists are needed.
长按识别下方二维码
立即加入肿瘤患者交流群
END
关注胃爱同行
了解胃癌知识
